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Publication : Tim3 binding to galectin-9 stimulates antimicrobial immunity.

First Author  Jayaraman P Year  2010
Journal  J Exp Med Volume  207
Issue  11 Pages  2343-54
PubMed ID  20937702 Mgi Jnum  J:166066
Mgi Id  MGI:4839671 Doi  10.1084/jem.20100687
Citation  Jayaraman P, et al. (2010) Tim3 binding to galectin-9 stimulates antimicrobial immunity. J Exp Med 207(11):2343-54
abstractText  T cell immunoglobulin and mucin domain 3 (Tim3) is a negative regulatory molecule that inhibits effector T(H)1-type responses. Such inhibitory signals prevent unintended tissue inflammation, but can be detrimental if they lead to premature T cell exhaustion. Although the role of Tim3 in autoimmunity has been extensively studied, whether Tim3 regulates antimicrobial immunity has not been explored. Here, we show that Tim3 expressed on T(H)1 cells interacts with its ligand, galectin-9 (Gal9), which is expressed by Mycobacterium tuberculosis-infected macrophages to restrict intracellular bacterial growth. Tim3-Gal9 interaction leads to macrophage activation and stimulates bactericidal activity by inducing caspase-1-dependent IL-1beta secretion. We propose that the T(H)1 cell surface molecule Tim3 has evolved to inhibit growth of intracellular pathogens via its ligand Gal9, which in turn inhibits expansion of effector T(H)1 cells to prevent further tissue inflammation.
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